The lagomorph infecting Treponema paraluisleporidarum is a close relative of the human syphilis-bacterium Treponema pallidum. There is a paucity of information on the epidemiology of hare syphilis and its relationship to the rabbit- and human-infecting treponemes that cause syphilis. In our study, we tested 734 serum samples from European brown hares (Lepus europaeus) collected between 2007 and 2019 in the federal state of Lower Saxony, Germany, for the presence of antibodies against Treponema paraluisleporidarum. Since T. paraluisleporidarum cross-reacts with T. pallidum antigen, we used a commercially available Treponema pallidum particle agglutination (TPPA) to test for the presence of antibodies. A high seropositivity (n = 405/734) was detected. An additional 233 serum samples were retested using a fluorescent treponemal antibody absorption test to confirm the results of the TPPA assay. Our results show that infection is widespread in Lower Saxony and suggest a horizontal (sexual) transmission mode since adult hares show significantly higher seropositivity than juveniles (odds ratio 0.03 [95% CI 0.02-0.05], p  less then  .0001). No difference was detected based on gender (odds ratio 0.79 [95% Cl 0.58-1.07], p = .1283). Further studies are warranted to genetically characterise the T. paraluisleporidarum strains that infect wild hares. This article is protected by copyright. All rights reserved.Glucose is the most abundant monosaccharide, and an essential source of energy for most living cells. Glucose transport across the cell membrane is mediated by two types of transporters facilitative glucose transporters (GLUTs, gene name solute-carrier (SLC)2A) and sodium glucose co-transporters (SGLTs, gene name SLC5A). Each transporter has its own substrate specificity, distribution, and regulatory mechanisms. Recently, sodium glucose co-transporter (SGLT)1 and SGLT2 have attracted **** attention as therapeutic targets for various diseases. This review addresses the basal and functional properties of GLUTs and SGLTs and describes the pharmaceutical potential of SGLT1 and SGLT2. This article is protected by copyright. All rights reserved.Ataluren promotes ribosomal readthrough of premature termination codons in mRNA which result from nonsense mutations. In vitro studies were performed to characterize the metabolism and enzyme kinetics of ataluren and its interaction potential with CYP enzymes. Incubation of [14 C]-ataluren with human liver microsomes indicated that the major metabolic pathway for ataluren is via direct glucuronidation and that the drug is not metabolized via cytochrome P450 (CYP). Glucuronidation was also observed in the incubation in human intestinal and kidney microsomes, but not in human pulmonary microsomes. UGT1A9 was found to be the major uridine diphosphate glucuronosyltransferase (UGT) responsible for ataluren glucuronidation in the liver and kidney microsomes. https://www.selleckchem.com/products/a-674563.html Enzyme kinetic analysis of the formation of ataluren acyl glucuronide, performed in human liver, kidney, and intestinal microsomes and recombinant human UGT1A9, found that increasing bovine serum albumin (BSA) levels enhanced the glucuronidation Michaelis-Menten constant (Km ) and ataluren protein binding but had a minimal effect on maximum velocity (Vmax ) of glucuronidation. Due to the decreased unbound Michaelis-Menten constant (Km,u ), the ataluren unbound intrinsic clearance (CLint,u ) increased for all experimental systems and BSA concentrations. Human kidney microsomes were about 3.7-fold more active than human liver microsomes, in terms of CLint,u /mg protein, indicating that the kidney is also a key organ for the metabolism and disposition of ataluren in humans. Ataluren showed no or little potential to inhibit or induce most of the CYP enzymes. © 2020 The Authors. Pharmacology Research & Perspectives published by John Wiley & Sons Ltd, British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics.BACKGROUND Although 18 F-FDG-PET/CT is a widely used diagnostic tool for several malignancies, its efficacy in diagnosing pancreatic neuroendocrine tumors is reported to be controversial because of the short-term follow-up. METHODS We retrospectively compared demographics and pathological features between 18 F-FDG-positive and -negative diseases. Additionally, we evaluated whether the avidity of 18 F-FDG-PET/CT affected earlier recurrence after curative treatment of non-functioning tumors. The median duration of observation was 65.6 months. RESULTS Seventy-two patients were enrolled. 18 F-FDG-positive diseases were pathologically advanced and significantly associated with metastatic behavior. In a multivariate analysis, metastatic behavior and WHO tumor grade was independently associated with 18 F-FDG accumulation. Only 25% of functional tumors (4/16) and 8% of insulinomas (1/12) were 18 F-FDG-positive. In a Kaplan-Meier analysis in patients with non-functioning tumors (n=56), 18 F-FDG positivity was significantly correlated with poorer recurrence-free survival (RFS) but had no correlation with overall survival.. In univariate analysis of factors associated with shorter RFS, male gender, prevalence of nodal metastasis, WHO tumor grade≥G2, or 18 F-FDG-positive disease were significantly higher in patients with shorter RFS, whereas only 18 F-FDG-positivity was associated with shorter RFS in multivariate analyses. CONCLUSIONS The avidity of 18 F-FDG-PET/CT was associated with metastatic behavior of pancreatic neuroendocrine tumors and recurrence after treatment of non-functioning tumors. This article is protected by copyright. All rights reserved.AIM The aim of this study was to explore shared decision-making among residents, their families and staff to determine relevant strategies to support shared decision-making in long-term care (LTC). BACKGROUND Meaningful engagement of long-term care home (LTCH) residents and their families in care decisions is key in the provision of quality of care. Shared decision-making is an interprofessional approach to increasing resident and family engagement in care decisions which can lead to higher quality decisions, more relevant care interventions and greater resident, family, and staff satisfaction. Despite these advantages, shared decision-making has not been widely implemented in practice in LTC. METHODS The study took place in one LTCH in Toronto, Ontario, Canada. A qualitative descriptive design was used to explore how residents, family members and staff described how they collaborate when making decisions concerning resident care, and their perceptions of facilitators and challenges to a collaborative approach to decision-making.
The lagomorph infecting Treponema paraluisleporidarum is a close relative of the human syphilis-bacterium Treponema pallidum. There is a paucity of information on the epidemiology of hare syphilis and its relationship to the rabbit- and human-infecting treponemes that cause syphilis. In our study, we tested 734 serum samples from European brown hares (Lepus europaeus) collected between 2007 and 2019 in the federal state of Lower Saxony, Germany, for the presence of antibodies against Treponema paraluisleporidarum. Since T. paraluisleporidarum cross-reacts with T. pallidum antigen, we used a commercially available Treponema pallidum particle agglutination (TPPA) to test for the presence of antibodies. A high seropositivity (n = 405/734) was detected. An additional 233 serum samples were retested using a fluorescent treponemal antibody absorption test to confirm the results of the TPPA assay. Our results show that infection is widespread in Lower Saxony and suggest a horizontal (sexual) transmission mode since adult hares show significantly higher seropositivity than juveniles (odds ratio 0.03 [95% CI 0.02-0.05], p  less then  .0001). No difference was detected based on gender (odds ratio 0.79 [95% Cl 0.58-1.07], p = .1283). Further studies are warranted to genetically characterise the T. paraluisleporidarum strains that infect wild hares. This article is protected by copyright. All rights reserved.Glucose is the most abundant monosaccharide, and an essential source of energy for most living cells. Glucose transport across the cell membrane is mediated by two types of transporters facilitative glucose transporters (GLUTs, gene name solute-carrier (SLC)2A) and sodium glucose co-transporters (SGLTs, gene name SLC5A). Each transporter has its own substrate specificity, distribution, and regulatory mechanisms. Recently, sodium glucose co-transporter (SGLT)1 and SGLT2 have attracted much attention as therapeutic targets for various diseases. This review addresses the basal and functional properties of GLUTs and SGLTs and describes the pharmaceutical potential of SGLT1 and SGLT2. This article is protected by copyright. All rights reserved.Ataluren promotes ribosomal readthrough of premature termination codons in mRNA which result from nonsense mutations. In vitro studies were performed to characterize the metabolism and enzyme kinetics of ataluren and its interaction potential with CYP enzymes. Incubation of [14 C]-ataluren with human liver microsomes indicated that the major metabolic pathway for ataluren is via direct glucuronidation and that the drug is not metabolized via cytochrome P450 (CYP). Glucuronidation was also observed in the incubation in human intestinal and kidney microsomes, but not in human pulmonary microsomes. UGT1A9 was found to be the major uridine diphosphate glucuronosyltransferase (UGT) responsible for ataluren glucuronidation in the liver and kidney microsomes. https://www.selleckchem.com/products/a-674563.html Enzyme kinetic analysis of the formation of ataluren acyl glucuronide, performed in human liver, kidney, and intestinal microsomes and recombinant human UGT1A9, found that increasing bovine serum albumin (BSA) levels enhanced the glucuronidation Michaelis-Menten constant (Km ) and ataluren protein binding but had a minimal effect on maximum velocity (Vmax ) of glucuronidation. Due to the decreased unbound Michaelis-Menten constant (Km,u ), the ataluren unbound intrinsic clearance (CLint,u ) increased for all experimental systems and BSA concentrations. Human kidney microsomes were about 3.7-fold more active than human liver microsomes, in terms of CLint,u /mg protein, indicating that the kidney is also a key organ for the metabolism and disposition of ataluren in humans. Ataluren showed no or little potential to inhibit or induce most of the CYP enzymes. © 2020 The Authors. Pharmacology Research & Perspectives published by John Wiley & Sons Ltd, British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics.BACKGROUND Although 18 F-FDG-PET/CT is a widely used diagnostic tool for several malignancies, its efficacy in diagnosing pancreatic neuroendocrine tumors is reported to be controversial because of the short-term follow-up. METHODS We retrospectively compared demographics and pathological features between 18 F-FDG-positive and -negative diseases. Additionally, we evaluated whether the avidity of 18 F-FDG-PET/CT affected earlier recurrence after curative treatment of non-functioning tumors. The median duration of observation was 65.6 months. RESULTS Seventy-two patients were enrolled. 18 F-FDG-positive diseases were pathologically advanced and significantly associated with metastatic behavior. In a multivariate analysis, metastatic behavior and WHO tumor grade was independently associated with 18 F-FDG accumulation. Only 25% of functional tumors (4/16) and 8% of insulinomas (1/12) were 18 F-FDG-positive. In a Kaplan-Meier analysis in patients with non-functioning tumors (n=56), 18 F-FDG positivity was significantly correlated with poorer recurrence-free survival (RFS) but had no correlation with overall survival.. In univariate analysis of factors associated with shorter RFS, male gender, prevalence of nodal metastasis, WHO tumor grade≥G2, or 18 F-FDG-positive disease were significantly higher in patients with shorter RFS, whereas only 18 F-FDG-positivity was associated with shorter RFS in multivariate analyses. CONCLUSIONS The avidity of 18 F-FDG-PET/CT was associated with metastatic behavior of pancreatic neuroendocrine tumors and recurrence after treatment of non-functioning tumors. This article is protected by copyright. All rights reserved.AIM The aim of this study was to explore shared decision-making among residents, their families and staff to determine relevant strategies to support shared decision-making in long-term care (LTC). BACKGROUND Meaningful engagement of long-term care home (LTCH) residents and their families in care decisions is key in the provision of quality of care. Shared decision-making is an interprofessional approach to increasing resident and family engagement in care decisions which can lead to higher quality decisions, more relevant care interventions and greater resident, family, and staff satisfaction. Despite these advantages, shared decision-making has not been widely implemented in practice in LTC. METHODS The study took place in one LTCH in Toronto, Ontario, Canada. A qualitative descriptive design was used to explore how residents, family members and staff described how they collaborate when making decisions concerning resident care, and their perceptions of facilitators and challenges to a collaborative approach to decision-making.
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